NIPPOSTRONGYLUS-BRASILIENSIS INFECTION EVOKES NEURONAL ABNORMALITIES AND ALTERATIONS IN NEURALLY REGULATED ELECTROLYTE TRANSPORT IN RAT JEJUNUM

Neuronal abnormalities have been described in the intestine of helmint h-infected rats. However, the physiological ramifications of these cha nges have not been determined. Here, we examined epithelial ion secret ion, indicated by increases in short-circuit current (Isc), evoked by electrical transmural stimulation (TS) of enteric nerves in Ussing-cha mbered jejunal tissues from Nippostrongylus brasiliensis-infected rats . Rats were examined at 10 and 35 days post-infection (p.i.); non-infe cted rats served as controls. TS resulted in significantly reduced ion secretion in jejunum from 10 day p.i. rats compared to controls or je junum from 35 day p.i. rats. The TS response in tissue from infected r ats had, unlike controls, no cholinergic component. Tissues from both non-infected and infected rats were equally responsive to the muscarin ic agonist bethanechol, suggesting that the cholinergic defect was neu ronal and not an inability of the epithelium to respond to cholinergic stimulation. However, increases in Isc evoked by exogenous substance P (SP) in tissue from rats 10 day p.i. were reduced in magnitude to ap proximately 25% of control values. Concomitant with these physiologica l changes, tissue from infected rats contained increased amounts of su bstance P immunoreactivity and intestinal sections displayed increased numbers of substance P-immunoreactive nerve fibre profiles at both 10 and 35 days p.i. Thus, following N. brasiliensis infection there is a shift in the enteric nervous system away from cholinergic to non-chol inergic regulation, associated with increased amounts of the pro-infla mmatory neuropeptide, substance P. We speculate that changes in neuron al structure and function are intimately involved in the co-ordinated multicellular response to intestinal parasitic infection and subsequen t gut recovery.